1. Field of the Invention
This invention pertains to methods and apparatus for monitoring the blood glucose level in biological tissues. It is especially useful for non-invasive monitoring of blood glucose in human or animal diabetics. Specifically, it relates to methods and apparatus for non-invasive monitoring of blood glucose using optical coherence interferometry with continuous area scanning and simultaneous depth scanning to reduce the effect of speckle (noise).
2. Description of the Related Art
Monitoring of blood glucose (blood sugar) concentration levels has long been critical to the treatment of diabetes in humans. Current blood glucose monitors involve a chemical reaction between blood serum and a test strip, requiring an invasive extraction of blood via a lancet or pinprick. Small handheld monitors have been developed to enable a patient to perform this procedure anywhere, at any time. But the inconvenience of this procedure—specifically the blood extraction and the use and disposition of test strips—has led to a low level of compliance. Such low compliance can lead to serious medical complications. Thus, a non-invasive method for monitoring blood glucose is needed.
Studies have shown that optical methods can detect small changes in biological tissue scattering related to changes in levels of blood sugar. Although highly complex, a first order approximation of monochromatic light scattered by biological tissue can be described by the following simplified equation:IR=IOexp[−(μa+μs)L]
where IR is the intensity of light reflected from the skin, IO is the intensity of the light illuminating the skin, μa is the absorption coefficient of the skin at the specific wavelength of light, μs is the scatter coefficient of the skin at the specific wavelength of light, and L is the total path traversed by the light. From this relationship it can be seen that the intensity of the light decays exponentially as either the absorption or the scattering of the tissue increases.
It is well established that there is a difference in the index of refraction between blood serum/interstitial fluid (blood/IF) and membranes of cells such as blood cells and skin cells. (See, R. C. Weast, ed., CRC Handbook of Chemistry and Physics, 70th ed., (CRC Cleveland, Ohio 1989)). This difference can produce characteristic scattering of transmitted light. Glucose, in its varying forms, is a major constituent of blood/IF. The variation of glucose levels in blood/IF changes its refractive index and thus, the characteristic scattering from blood-perfused tissue. In the near infrared wavelength range (NIR), blood glucose changes the scattering coefficient more than it changes the absorption coefficient. Thus, the optical scattering of the blood/IF and cell mixture varies as the blood glucose level changes. Accordingly, an optical method has potential for non-invasive measurement of blood glucose concentration.
Non-invasive optical techniques being explored for blood glucose application include polarimetry, Raman spectroscopy, near-infrared absorption, scattering spectroscopy, photoacoustics and optoacoustics. Despite significant efforts, these techniques have shortcomings such as low sensitivity, low accuracy (less than current invasive home monitors) and insufficient specificity of glucose concentration measurement within the relevant physiological range (4-30 mM or 72-540 mg/dL). Accordingly, there is a need for an improved method to non-invasively monitor glucose.
Optical coherence tomography, or OCT, is an optical imaging technique using light waves that produces high resolution imagery of biological tissue. OCT creates its images by interferometrically scanning in depth a linear succession of spots, and measuring absorption and/or scattering at different depths in each successive spot. The data is then processed to present an image of the linear cross section. It has been proposed that OCT might be useful in measuring blood glucose.
There are, however, major drawbacks to the use of OCT for glucose monitoring. First, the OCT process requires lengthy scanning to reduce optical noise (“speckle”). Speckle arises from wavefront distortion, when coherent light scatters from tissue. OCT seeks to minimize speckle by averaging it out over many measurements. However this approach in OCT requires a time period impractically long for a home monitor, and even then speckle in OCT remains problematic for achieving a sufficiently accurate measurement of glucose level.
A second drawback of OCT is that it requires complex processing to form an image and even further processing to analyze the image data to determine glucose levels.
A third drawback is that OCT requires expensive, bulky, precision equipment neither suitable for transport or for use outside the laboratory. Accordingly, there is a need for an improved methods and apparatus for non-invasive blood glucose monitoring.